Use of chlorprothixene and the risk of diabetes and major adverse cardiovascular events: A nationwide cohort study

Mikkel Højlund*, Christina Blanner Wagner, Rikke Wesselhoeft, Kjeld Andersen, Anders Fink-Jensen, Jesper Hallas

*Kontaktforfatter for dette arbejde

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Abstrakt

Chlorprothixene is commonly used off-label in low doses for sedative-hypnotic purposes although it might carry a risk of cardiometabolic adverse events due to its pharmacodynamic profile. We investigated the risk of diabetes and major adverse cardiovascular events (MACE) with use of low-dose chlorprothixene, compared with use of low-dose quetiapine in a nationwide cohort study, including all new users of low-dose chlorprothixene (n = 81 328) and low-dose quetiapine (n = 91 163) in Denmark 2000–2017. Main outcomes were diabetes and MACE (myocardial infarction, stroke and death from cardiovascular causes). The association between cumulative dose of chlorprothixene and the outcomes was tested in a case–control analysis. Low-dose chlorprothixene use was associated with increased risk of diabetes (intention-to-treat [ITT]-hazard ratio [HR]: 1.16; 95% CI: 1.08–1.25), compared with low-dose quetiapine use. This association strengthened when follow-up was restricted to time on treatment (as-treated [AT]-HR: 1.34; 95% CI: 1.14–1.56). Low-dose chlorprothixene use was also associated with increased risk of MACE (ITT-HR: 1.12; 95% CI: 1.04–1.21) and stroke (ITT-HR: 1.21; 95% CI: 1.06–1.37) but not with myocardial infarction (ITT-HR: 1.11; 95% CI: 0.95–1.30) nor death from cardiovascular causes (ITT-HR: 1.07; 95% CI: 0.96–1.20). Cumulative dose of chlorprothixene ≥6000 mg was associated with increased risk of diabetes (OR: 1.15–1.63; test for trend: p < 0.001), whereas cumulative dose of chlorprothixene ≥1500 mg was associated with increased risk of MACE (OR: 1.10–1.85; test for trend: p < 0.001). In conclusion, low-dose chlorprothixene use is associated with increased risk of cardiometabolic adverse events compared with low-dose quetiapine use.

OriginalsprogEngelsk
TidsskriftBasic and Clinical Pharmacology and Toxicology
Vol/bind130
Udgave nummer4
Sider (fra-til)501-512
ISSN1742-7835
DOI
StatusUdgivet - apr. 2022

Bibliografisk note

Funding Information:
This study was supported by Mental Health Services in the Region of Southern Denmark (grant number A2957).

Publisher Copyright:
© 2022 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

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